Atypical movement disorders in the early stages of Huntington's disease: clinical and genetic analysis

Abstract

Huntington's disease (HD) is notably difficult to diagnose in the early stages. One reason is that the early clinical manifestations of HD vary widely and sometimes have an atypical onset. In this paper we primarily sought information on affected patients who initially presented with movement disorders other than chorea. We also investigated atypical motor presentations in relation to triplet CAG expansions. After reviewing the clinical records of two neurological centres, we identified patients with a final, documented diagnosis of HD and selected for study 205 patients according to their onset of motor manifestations. CAG repeats were analysed. Of the 205 patients studied, 15 had atypical motor symptoms at onset. In this group we identified three types of initial clinical manifestations other than chorea: parkinsonism, ataxia and dystonia. We conclude that HD patients may have different motor manifestations at the initiation of the illness. Patients with atypical movement disorders in the early stages have larger CAG expansions and an earlier age at onset than HD patients with typical onset chorea.

The gender effect in juvenile Huntington disease patients of Italian origin

“…Patients presenting with rigidity as the initial symptom of HD showed a significantly longer CAG repeat expansion than patients with clinical features of chorea at onset. This finding confirms our previous observation [Squitieri et al, 2000b], in line with other poly(Q) diseases [Ikeuchi et al, 1995;Komure et al, 1995], underlying the occurrence of choreic features associated with shorter and, therefore, less toxic expanded mutations. Coherently, patients who initially presented with dystonia and no choreic movements manifested an earlier onset than their CAG repeat expansion led us to expect (Table I).…”

Low brain‐derived neurotrophic factor (BDNF) levels in serum of Huntington's disease patients

“…Dysfunction and degeneration of neurons in basal ganglia and in brain cortex lead to a neurological and psychiatric phenotype characterized by movement disorders and progressive dementia [Ciarmiello et al, 2006]. The interruption of excitatory connections from cerebral cortex to basal ganglia due to pyramidal cell loss in primary motor cortex, as well as reduced corticostriatal trophic support, may contribute to the development of neurological symptoms [Squitieri et al, 2000;Zuccato et al, 2001;MacDonald and Halliday, 2002]. Ample evidence describes reduced brainderived neurotrophic factor (BDNF) production and axonal cortical-striatal transportation in transgenic mice together with low BDNF levels in post-mortem human HD brains [Ferrer et al, 2000;Zuccato et al, 2001;Canals et al, 2004;Gauthier et al, 2004;Seo et al, 2004].…”

“…The study was approved by the Ethics Committees of IRCCS Istituto Auxologico Italiano and Neuromed, where a large databank was set up for clinical and genetic data of patients with HD [Squitieri et al, 2000]. After obtaining informed consent, we enrolled a cohort of 42 symptomatic patients with HD and 42 age-matched healthy subjects.…”

“…None of the patients or control subjects had a history of appreciable changes in the sleep-wake cycle. For neurological assessment we used the Unified Huntington's Disease Rating Scale (UHDRS) [Huntington Study Group, 1996], as described elsewhere [Squitieri et al, 2000[Squitieri et al, , 2003. The control group underwent detailed medical history-taking.…”

Multiagent imaging of the brain

“…Research models to date attempting to predict the age at onset in unaffected mutation carriers have merely sought to relate CAG expansion size to subject age [96]. Recently a new model for predicting the age at onset was reported: this model includes, along with CAG expansion and the subject's age, uptake of […”